title: Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study.
abstract: The possibility of using polysorbate 80-coated polybutylcyanoacrylate nanoparticles to deliver low molecular polar hydrophilic drugs to the CNS has been studied. Tubocurarine (a quaternary ammonium salt) does not penetrate the normal intact blood-brain barrier. However, the injection of this drug directly into the cerebral ventricles of the brain provokes the development of epileptiform seizures as assessed by electroencephalogram (EEG). An in situ perfused rat brain technique was used as an experimental technique together with a simultaneous recording of the EEG. Nanoparticles were prepared by butylcyanoacrylate polymerization in an acidic medium. Fifteen minutes after the introduction of tubocurarine-loaded polysorbate 80-coated nanoparticles into the perfusate, epileptiform spikes in the EEG appeared. Intraventricular injection of tubocurarine caused the appearance of the EEG seizures 5 min after administration. Neither tubocurarine solution nor tubocurarine-loaded nanoparticles without polysorbate 80 or a mixture of polysorbate 80 and tubocurarine were able to influence the EEG. Thus only the loading of tubocurarine onto the polysorbate 80-coated nanoparticles appears to enable the transport of this quaternary ammonium compound through the blood-brain barrier.
authors.affiliation: Department of Pharmacology, Sechenov Medical Academy, Moscow, Russia.
authors.forename: R N
authors.initials: RN
authors.lastname: Alyautdin
authors.forename: E B
authors.initials: EB
authors.lastname: Tezikov
authors.forename: P
authors.initials: P
authors.lastname: Ramge
authors.forename: D A
authors.initials: DA
authors.lastname: Kharkevich
authors.forename: D J
authors.initials: DJ
authors.lastname: Begley
authors.forename: J
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000327:Adsorption; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects*; D004659:Enbucrilate / Q000008:administration & dosage*; D005079:Excipients / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010316:Particle Size; D010477:Perfusion; D011136:Polysorbates / Q000008:administration & dosage*; D051381:Rats; D011912:Rats, Inbred ACI; D017208:Rats, Wistar; D012996:Solutions; D013535:Suspensions; D014403:Tubocurarine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D005079:Excipients; D018733:Nicotinic Antagonists; D011136:Polysorbates; D012996:Solutions; D013535:Suspensions; D004659:Enbucrilate; D014403:Tubocurarine